title: Analysis of transcriptional profiles and functional clustering of global cerebellar gene expression in PCD3J mice.
abstract: The Purkinje cell degeneration (PCD) mutant mouse is characterized by a degeneration of cerebellar Purkinje cells and progressive ataxia. To identify the molecular mechanisms that lead to the death of Purkinje neurons in PCD mice, we used Affymetrix microarray technology to compare cerebellar gene expression profiles in pcd3J mutant mice 14 days of age (prior to Purkinje cell loss) to unaffected littermates. Microarray analysis, Ingenuity Pathway Analysis (IPA) and expression analysis systematic explorer (EASE) software were used to identify biological and molecular pathways implicated in the progression of Purkinje cell degeneration. IPA analysis indicated that mutant pcd3J mice showed dysregulation of specific processes that may lead to Purkinje cell death, including several molecules known to control neuronal apoptosis such as Bad, CDK5 and PTEN. These findings demonstrate the usefulness of these powerful microarray analysis tools and have important implications for understanding the mechanisms of selective neuronal death and for developing therapeutic strategies to treat neurodegenerative disorders.
authors.affiliation: Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA; Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA. Electronic address: bford@msm.edu.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Ford
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Byron D
authors.initials: BD
authors.lastname: Ford
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Ernest C
authors.initials: EC
authors.lastname: Steele
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Alicia
authors.initials: A
authors.lastname: Gates
authors.affiliation: Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Darryl
authors.initials: D
authors.lastname: Hood
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Mika A B
authors.initials: MAB
authors.lastname: Matthews
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Mirza
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA.
authors.forename: Peter R
authors.initials: PR
authors.lastname: MacLeish
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020869:Gene Expression Profiling; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D014158:Transcription, Genetic